One claim is that the county was named for Thomas J. Holmes, who came from North Carolina to settle in the area about 1830.

He was subsequently killed in 1818 by a raiding party sent by Andrew Jackson during the First Seminole War.

The first was Hewett's Bluff (later renamed Bear Pen, then Cerro Gordo), then Pittman's Ferry, then Westville, and finally Bonifay.

Historic places in the county include: Ponce de Leon Springs State Park, Ponce de Leon According to the U.S. Census Bureau, the county has a total area of 489 square miles (1,270 km2), of which 479 square miles (1,240 km2) is land and 10 square miles (26 km2) (2.1%) is water.

The 2020 United States census counted 19,653 people, 7,282 households, and 4,778 families in Holmes County, Florida.

[15] The 2016-2020 5-year American Community Survey estimates show that the median household income was $39,215 (with a margin of error of +/- $3,549).

The so-called "Dominickers", a number of related mixed-race (white, black, and Euchee Indian) families, lived for decades after the Civil War and well into the twentieth century in a rural area near Ponce de Leon, with a separate church and segregated public elementary school.

The 1950 federal census identified 60 members of this group living in Holmes County at that time.

It gave the fifth-highest percentage of the vote for segregationist George Wallace of any county in the country during the 1968 election,[27] and apart from Deep South native Jimmy Carter, no Democrat since 1964 has obtained as much as thirty-four percent of the county's vote in any Presidential election.

It is located at 303 North J. Harvey Etheridge Street, Bonifay, Florida 32425.

The library is open Tuesday-Friday 8:00am–5:00pm, and Saturday 8:00am–12:00pm and offers public computers with internet access, free wi-fi, programming for all ages, and access to e-books, e-audiobooks, and numerous online databases and resources.

Holmes County is also a part of the Panhandle Public Library Cooperative System.

The primary one is the CSX P&A Subdivision, a line formerly owned by the Louisville and Nashville Railroad that served Amtrak's Sunset Limited.

The Georgiana Branch entered the state and county from Highnote, Alabama then ran through Esto and later Eleanor before crossing SR 2 and leaving the county towards Graceville and Campbellton, where it had a junction with the Bay Line Railroad.